A pathologist's analysis of histology images is primarily subjective. Since health care practice is evidence-based, it is crucial to have reproducible methods. The subjective nature of many diagnostic tasks in anatomic pathology and cytology is, however, known to cause reproducibility problems, i.e., high inter- and intra-observer variability in many diagnostic situations. See, Polley et al., An International Ki67 Reproducibility Study. JNCI Journal of the National Cancer Institute 105.24 (2013): 1897-1906. PMC. Web. 24 Nov. 2015.
Today there are many scanners capable of producing high-quality digital images from the microscopy glasses. The resulting images are very large, often 100,000×200,000 pixels. See, e.g., Rojo et al., Critical comparison of 31 commercially available slide systems in pathology, Int J Surg. Pathol., 2006; 14(4):285-305. This digital practice is often called “WSI” or “virtual microscopy” for cytopathology. The resulting digital images can be very large, for instance 30,000×40,000 pixels, 100,000×100,000 pixels or more. In histology, a two-dimensional (2D) image often suffices, but there is also the possibility to produce slices across the depth of the tissue section, creating a three-dimensional (3D) dataset even though the extent in the z direction can be far different from the x-y directions.
A key problem both for manual diagnostic review and automated image analysis is that there are substantial variations in the appearance of the WSI images. Diagnostic decisions are made on the basis of the image appearance, and patient treatment are to a high degree determined by subtle differences such as whether the percentage of positively stained cells are below or above a cut-off level.
One cause for the appearance variation is differences in the laboratory preparation of the glass slide, such as variations in staining (in the chemicals or in the handling) and variations stemming from the scanning. See, Laurinaviciene, Aida et al., Digital Immunohistochemistry Platform for the Staining Variation Monitoring Based on Integration of Image and Statistical Analyses with Laboratory Information System, Diagnostic Pathology 9.Suppl 1 (2014): S10. PMC. Web. 24 Nov. 2015; and Laurinavicius Arvydas et al., Digital immunohistochemistry: new horizons and practical solutions in breast cancer pathology, Diagnostic Pathology 2013, 8(Suppl 1):S15. Despite continuous efforts to address the inherent variations, they still remain a problem.
Between laboratories the differences are often more accentuated which is an increasing problem as modern healthcare often is based on external consultations and this is indeed a primary benefit of introducing a digital diagnostic paradigm in pathology. See, Polley et al., An International Ki67 Reproducibility Study, JNCI Journal of the National Cancer Institute 105.24 (2013): 1897-1906. PMC. Web. 24 Nov. 2015.
Thus, there remains a need for effective tools for the pathologist (the specialized diagnostic physician) to increase consistency and/or produce consistent assessments, despite varying images and subjectivity.